Abstract
Introduction: Thrombocytopenic purpura (TTP) is an extremely rare disease in children, yet potentially life-threatening without timely therapeutic plasma exchange (TPE). Gold standard for diagnosis is ADAMTS 13 activity </= 10, which may not be readily available, take days to result and delay treatment. PLASMIC score was devised and validated to make a presumptive diagnosis of TTP and initiate early intervention in adults with thrombotic microangiopathy (TMA). It allots one point for each variable for maximum score of 7, and is intended to be used only with thrombocytopenia (platelets < 150,000) and schistocytes on peripheral smear. The variables are thrombocytopenia (Platelets < 30,000/L), evidence of hemoLysis (reticulocyte count > 2.5%, haptoglobin undetectable, or indirect bilirubin > 2.0 mg/dL), absence of Active cancer (or no cancer treatment within the past year), no solid-organ or Stem-cell transplant, MCV < 90 fL, INR < 1.5, and Creatinine < 2.0 mg/dL. Patients with PLASMIC score of 0-4 considered low risk group with 0% risk, 5 as intermediate risk group with 6% risk, and 6 or 7 as high-risk group with 72% risk of severe ADAMTS-13 deficiency (activity < 10%). Patients in intermediate and high-risk group should start TPE while awaiting ADAMTS-13 activity levels.
All parameters could potentially be applied in children except serum creatinine. However, there is not enough data to validate the score in children. There are two pediatric case reports where PLASMIC score was used to support or predict TTP. Of note, age of the patients in these reports was 15 - 16 years, and PLASMIC score was used without modifications. In an adult, creatinine of 2 mg/dL would roughly be 50% reduction in renal function, but could indicate severe kidney dysfunction in children, especially the young. Therefore, an estimated glomerular filtration rate (eGFR) would be a better parameter for kidney function in children. We modified the PLASMIC score (PLASMICkid) with eGFR > 50ml/min/1.73m2 substituting serum creatinine < 2 mg/dL. We aimed to assess the applicability of our PLASMICkid score in pediatric patients with TTP.
Methods: We identified patients ≤ 19 years of age with TTP and patients who received TPE for diagnosis of TMA from 2010 to 2021 via an administrative database and performed retrospective chart review. Patients who did not have one or more parameters to calculate PLASMICkid score, or did not have ADAMTS-13 activity were excluded. Serum creatinine based revised bedside Schwartz equation was used to calculate eGFR, to be used in place of serum creatinine. A similar scoring system as the original score retaining rest of the parameters, was used to stratify risk for TTP.
Results: We had a total of 30 patients who met the inclusion criteria, with a mean age of 9 years (range 11 months to 19 years). Severe ADAMTS-13 deficiency with activity level ≤10% was noted in 14/30 patients. All patients with severe deficiency had scores of 6 or 7 with 100% sensitivity (p-value 0.002, Table). Interestingly, we could apply it to a child as young as 11 months with an ADAMTS-13 activity of 10%, who had a score of 5 indicating intermediate risk for TTP. It also showed 100% negative predictive value, with 8/8 patients with a score of 0-4 having normal ADAMTS-13 activity.
Conclusion: This is the first study to our knowledge that has attempted to modify the PLASMIC score for pediatric population. None of the patients with TTP had a PLASMICkid score of < 5 making it a fairly sensitive tool in presumptive diagnosis of pediatric TTP. PLASMICkid would need validation in larger cohorts, however using eGFR instead of serum creatinine in PLASMIC score can increase sensitivity in identifying high risk pediatric patients needing early TPE.
Disclosures
Sartain:Alexion, Azra Zeneca Rare Disease: Research Funding.
